An endotoxin-induced serum factor that causes necrosis of tumors

Proc Natl Acad Sci U S A. 1975 Sep;72(9):3666-70. doi: 10.1073/pnas.72.9.3666.


In studying "hemorrhagic necrosis" of tumors produced by endotoxin, it was found that the serum of bacillus Calmette--Guerin (BCG)-infected mice treated with endotoxin contains a substance (tumor necrosis factor; TNF) which mimics the tumor necrotic action of endotoxin itself. TNF-positive serum is as effective as endotoxin itself in causing necrosis of the sarcoma Meth A and other transplanted tumors. A variety of tests indicate that TNF is not residual endotoxin, but a factor released from host cells, probably macrophages, by endotoxin. Corynebacteria and Zymosan, which like BCG induce hyperplasia of the reticulo-endothelial system, can substitute for BCG in priming mice for release of TNF by endotoxin. TNF is toxic in vitro for two neoplastic cell lines; it is not toxic for mouse embryo cultures. We propose that TNF mediates endotoxin-induced tumor necrosis, and that it may be responsible for the suppression of transformed cells by activated macrophages.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adjuvants, Immunologic
  • Animals
  • BCG Vaccine*
  • Dose-Response Relationship, Drug
  • Endotoxins / pharmacology
  • Endotoxins / therapeutic use*
  • Immunotherapy
  • Leukemia, Experimental / immunology
  • Leukemia, Experimental / therapy
  • Macrophages / immunology*
  • Mice
  • Mycobacterium Infections / immunology
  • Mycobacterium bovis / immunology*
  • Necrosis
  • Sarcoma, Experimental / immunology*
  • Sarcoma, Experimental / therapy
  • Time Factors


  • Adjuvants, Immunologic
  • BCG Vaccine
  • Endotoxins